Summary of Study ST003300

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002050. The data can be accessed directly via it's Project DOI: 10.21228/M8MZ4N This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST003300
Study TitleHypothalamic SLC7A14 accounts for aging-reduced lipolysis in white adipose tissue
Study SummaryThe central nervous system has been implicated in the age-induced reduction in adipose tissue lipolysis. SLC7A14 is a lysosomal membrane protein highly expressed in the brain. Herein, we investigated the possible role of hypothalamic SLC7A14 in the age-induced lipolysis reduction. In this study, we demonstrated the expression of SLC7A14 was reduced in proopiomelanocortin (POMC) neurons of aged mice. Overexpression of SLC7A14 in POMC neurons alleviated the age-induced reduction in white adipose tissue (WAT) lipolysis, whereas SLC7A14 deletion mimicked the age-induced lipolysis impairment. Moreover, POMC SLC7A14 regulated WAT lipolysis independently of sympathetic nerves in WAT. Metabolomics analysis revealed that POMC SLC7A14 increased the primary bile acid taurochenodeoxycholic acid (TCDCA) content, which mediated the SLC7A14 knockout- or age-induced WAT lipolysis impairment. Furthermore, SLC7A14-increased TCDCA content is dependent on intestinal apical sodium-dependent bile acid transporter (ASBT), which is regulated by intestinal sympathetic afferent nerves. Finally, SLC7A14 regulated the intestinal sympathetic afferent nerves by inhibiting mTORC1 signaling through inhibiting TSC1 phosphorylation. Collectively, our study suggests the function for central SLC7A14 and an upstream mechanism for the mTORC1 signaling pathway. Moreover, our data provides insights into the brain–gut–adipose tissue crosstalk in age-induced lipolysis impairment.
Institute
Shanghai Institutes for Biological Sciences (SIBS) Chinese Academy of Sciences (CAS)
Last NameLiu
First NameKan
AddressNo. 320, Yueyang Road, Shanghai
Emailliukan2019@sibs.ac.cn
Phone021-17718134725
Submit Date2024-05-13
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2024-07-15
Release Version1
Kan Liu Kan Liu
https://dx.doi.org/10.21228/M8MZ4N
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR002050
Project DOI:doi: 10.21228/M8MZ4N
Project Title:Hypothalamic SLC7A14 accounts for aging-reduced lipolysis in white adipose tissue
Project Type:Mass spectrometry
Project Summary:The central nervous system has been implicated in the age-induced reduction in adipose tissue lipolysis. SLC7A14 is a lysosomal membrane protein highly expressed in the brain. Herein, we investigated the possible role of hypothalamic SLC7A14 in the age-induced lipolysis reduction. In this study, we demonstrated the expression of SLC7A14 was reduced in proopiomelanocortin (POMC) neurons of aged mice. Overexpression of SLC7A14 in POMC neurons alleviated the age-induced reduction in white adipose tissue (WAT) lipolysis, whereas SLC7A14 deletion mimicked the age-induced lipolysis impairment. Moreover, POMC SLC7A14 regulated WAT lipolysis independently of sympathetic nerves in WAT. Metabolomics analysis revealed that POMC SLC7A14 increased the primary bile acid taurochenodeoxycholic acid (TCDCA) content, which mediated the SLC7A14 knockout- or age-induced WAT lipolysis impairment. Furthermore, SLC7A14-increased TCDCA content is dependent on intestinal apical sodium-dependent bile acid transporter (ASBT), which is regulated by intestinal sympathetic afferent nerves. Finally, SLC7A14 regulated the intestinal sympathetic afferent nerves by inhibiting mTORC1 signaling through inhibiting TSC1 phosphorylation. Collectively, our study suggests the function for central SLC7A14 and an upstream mechanism for the mTORC1 signaling pathway. Moreover, our data provides insights into the brain–gut–adipose tissue crosstalk in age-induced lipolysis impairment.
Institute:Shanghai Institutes for Biological Sciences (SIBS) Chinese Academy of Sciences (CAS)
Last Name:Liu
First Name:Kan
Address:No. 320, Yueyang Road, Shanghai, Shanghai, Shanghai/Shanghai/xuhui, 200000, China
Email:liukan2019@sibs.ac.cn
Phone:021-17718134725

Subject:

Subject ID:SU003421
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Gender:Male

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Sample source Genotype Treatment
SA358120QC2Blood serum QC control
SA358121QC1Blood serum QC control
SA358122QC3Blood serum QC control
SA358123oe1Blood serum SLC7A14_OE control
SA358124oe2Blood serum SLC7A15_OE control
SA358125oe3Blood serum SLC7A16_OE control
SA358126oe4Blood serum SLC7A17_OE control
SA358127control3Blood serum WT control
SA358128control1Blood serum WT control
SA358129control2Blood serum WT control
SA358130control4Blood serum WT control
SA358131control5Blood serum WT control
Showing results 1 to 12 of 12

Collection:

Collection ID:CO003414
Collection Summary:Blood was collected from control or overexpression of SLC7A14 in POMC neuron mice.Blood sample was collected into a BD Vacutainer tube not containing any anticoagulant, which was allowed to sit for ~30–60 min for clots to form following which serum was obtained by centrifugation (15 min at 4°C at 3500 rpm).
Sample Type:Blood (serum)

Treatment:

Treatment ID:TR003430
Treatment Summary:To overexpression of SLC7A14 in ARC POMC neurons, POMC Cre mice were bilaterally injected either with a Cre-dependent AAV vector containing SLC7A14 in the opposite orientation flanked by two inverted loxP sites (AAV9-Syn-DIO-SLC7A14-mCherry, 1.5 × 1012 Pfu/mL, HANBIO) at a volume of 200 nL into the ARC or an AAV vector containing only mCherry in the opposite orientation flanked by two inverted loxP sites (AAV9-Syn-DIO-mCherry, 1.5 × 1012 Pfu/mL, HANBIO) as a control. Serum was collected from control or overexpression of SLC7A14 in POMC neuron mice.

Sample Preparation:

Sampleprep ID:SP003428
Sampleprep Summary:The samples (100 μL) were placed in the EP tubes and resuspended with prechilled 80% methanol and 0.1% formic acid by well vortex. Then the sampleswere incubated on ice for 5 min and centrifuged at 15,000 g, 4°C for 20 min. Some of supernatant was diluted to final concentration containing 53% methanol by LC-MS grade water.The samples were subsequently transferred to a fresh Eppendorf tube and then were centrifuged at 15000 g, 4°C for 20 min. Finally, the supernatant was injected into the LC-MS/MS system analysis

Combined analysis:

Analysis ID AN005407
Analysis type MS
Chromatography type Reversed phase
Chromatography system Thermo Vanquish
Column Thermo Hypersil GOLD aQ (100 x 2.1mm,1.9um)
MS Type ESI
MS instrument type Orbitrap
MS instrument name Thermo Q Exactive HF-X Orbitrap
Ion Mode NEGATIVE
Units Peak area

Chromatography:

Chromatography ID:CH004100
Instrument Name:Thermo Vanquish
Column Name:Thermo Hypersil GOLD aQ (100 x 2.1mm,1.9um)
Column Temperature:40°C
Flow Gradient:2% B, 1.5 min; 2-100% B, 12.0 min; 100% B, 14.0 min;100-2% B, 14.1 min;2% B, 17 min.
Flow Rate:0.2 mL/min
Solvent A:100% Water; 5mM Ammonium acetate
Solvent B:100% Methanol
Chromatography Type:Reversed phase

MS:

MS ID:MS005134
Analysis ID:AN005407
Instrument Name:Thermo Q Exactive HF-X Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:The raw data files generated by UHPLC-MS/MS were processed using the Compound Discoverer 3.1 (CD3.1, ThermoFisher) to perform peak alignment, peak picking, and quantitation for each metabolite. The main parameterswere set as follows: retention time tolerance, 0.2 minutes; actual mass tolerance, 5ppm; signal intensity tolerance, 30%; signal/noise ratio, 3; and minimum intensity, et al. After that, peak intensities were normalized to the total spectral intensity.The normalized data was used to predict the molecular formula based on additive ions, molecular ion peaks and fragment ions. And then peaks were matched with the mzCloud (https://www.mzcloud.org/),mzVault and MassList database to obtain the accurate qualitative and relative quantitative results.Statistical analyses were performed using the statistical software R (R version R-3.4.3),Python (Python 2.7.6 version) and CentOS (CentOS release 6.6),When data were not normally distributed, normal transformations were attempted using of area normalization method.
Ion Mode:NEGATIVE
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